Related Experiment Video
Updated: May 5, 2026
Site-Directed Immobilization of Bone Morphogenetic Protein 2 to Solid Surfaces by Click Chemistry
Published on: March 29, 2018
Localized therapeutic strategy based on microRNA-21-loaded mesoporous silica nanoparticles hydrogel improves bone
Ye Li1,2, Siyuan Huang1,2, Yihan Xing1,2
1Hospital of Stomatology, Guanghua School of Stomatology, Institute of Stomatological Research, Sun Yat-Sen University, Guangzhou, 510000, Guangdong, China.
Background:
Medication-related osteonecrosis of the jaw (MRONJ), caused by long-term anti-resorptive therapy, leads to bone necrosis and impaired healing. This study developed a miR-21-loaded mesoporous silica nanoparticles (MSN) hydrogel to promote local bone regeneration.
Methods:
Transcriptome sequencing of zoledronic acid (ZOL)-treated osteoclasts (OCs) revealed PDCD4 upregulation and NF-κB (p65) phosphorylation inhibition. miR-21, identified as a regulator of PDCD4, was validated in vitro. Amino-modified mesoporous silica nanoparticles (MSN-NH₂) were synthesized to carry miR-21, and embedded in a dynamic Schiff base-crosslinked hydrogel. The hydrogel's biocompatibility, sustained release, and therapeutic effect were evaluated in a rat MRONJ model via micro-CT, histology, TRAP staining, and RNA in situ hybridization (RISH).
Results:
miR-21 reversed ZOL-induced suppression of NF-κB/p65 phosphorylation by targeting PDCD4, thereby restoring osteoclast differentiation and resorption activity. The miR-21-loaded MSN hydrogel promoted bone regeneration, increased TRAP⁺ osteoclast numbers, and elevated local miR-21 expression, while maintaining systemic safety. These findings suggest that the miR-21-loaded MSN hydrogel system exerts its therapeutic effect primarily through the miR-21/PDCD4/NF-κB signaling pathway, facilitating coordinated regulation of osteoclast-mediated bone remodeling.
Conclusions:
The miR-21-loaded MSN hydrogel effectively restored bone remodeling and healed MRONJ defects without systemic toxicity, offering a promising localized adjunct to anti-resorptive therapies.
